1. Field of the Invention
This invention relates to non-invasive methods for monitoring a patient's vascular volume during renal replacement therapy by means of at least one pulse oximetry/photoplethysmography sensors. Further, this invention relates to monitoring a patient's vascular volume, vascular tone, and/or regional blood flow (e.g. carotid blood flow as a surrogate for cerebral blood flow) during renal replacement therapy using photoplethysmography methods and adjusting the rate of ultrafiltration real-time during the patient's treatment.
2. Discussion of the Art
Renal Replacement Therapy (RRT) has evolved from the long, slow hemodialysis treatment regime of the 1960's to a diverse set of therapy options, the vast majority of which employ high permeability membrane devices and ultrafiltration control systems.
Biologic kidneys remove metabolic waste products, other toxins, and excess water. They also maintain electrolyte balance and produce several hormones for a human or other mammalian body. An artificial kidney, also called a hemodialyzer or dialyzer, and attendant equipment and supplies are designed to replace the blood-cleansing functions of the biologic kidney. At the center of artificial kidney design is a semipermeable filter membrane that allows passage of water, electrolytes, and solute toxins to be removed from the blood. The membrane retains in the blood, the blood cells, plasma proteins and other larger elements of the blood.
Over the last 15 years, the intended use of the RRT has evolved into a subset of treatment alternatives that are tailored to individual patient needs. They include ultrafiltration, hemodialysis, hemofiltration, and hemodiafiltration, all of which are delivered in a renal care environment, as well as hemoconcentration, which is typically delivered in open heart surgery. Renal replacement therapies may be performed either intermittently or continuously, in the acute or chronic renal setting, depending on the individual patient's needs.
Ultrafiltration involves the removal of excess fluid from the patient's blood by employing a pressure gradient across a semipermeable membrane of a high permeability hemofilter or dialyzer. For example, removal of excess fluid occurs in hemoconcentration at the conclusion of cardiopulmonary bypass surgery. Hemodialysis involves the removal of toxins from the patient's blood by employing diffusive transport through the semipermeable membrane, and requires an electrolyte solution (dialysate) flowing on the opposite side of the membrane to create a concentration gradient. A goal of dialysis is the removal of waste, toxic substances, and/or excess water from the patients' blood. Dialysis patients require removal of excess water from their blood because they lack the ability to rid their bodies of fluid through normal kidney function.
One of the potential risks to health associated with RRT is hypotension, which is an abnormal decrease in the patient's blood pressure. An abnormally high or uncontrolled ultrafiltration rate may result in hypovolemic shock, hypotension, or both. If too much water is removed from the patient's vascular compartment, such as might occur if the ultrafiltration rate is too high or uncontrolled, the patient could suffer hypotension and/or go into hypovolemic shock. Accordingly, RRT treatments must be controlled to prevent hypotension.
Rapid reduction in plasma or blood volume due to excessive ultrafiltration of water from blood may cause a patient to exhibit one or more of the following symptoms: hypovolemia-hypotension, diaphoresis, cramps, nausea, or vomiting. During treatment, vascular volume in the patient's blood would theoretically remain constant if the plasma refilling rate equaled the ultrafiltration rate. However, refilling of the plasma is often not completed during a RRT session. The delay in refilling the plasma can lead to insufficient blood volume in a patient.
There appears to be a “critical” blood volume value below which patients begin to have problems associated with hypovolemia (abnormally decreased blood volume). Fluid replenishing rate is the rate at which the fluid (water and electrolytes) can be recruited from tissue into the blood stream across permeable walls of capillaries. This way blood volume is maintained relatively constant. Most of patients can recruit fluid at the rate of 500 to 1000 mL/hour. When patients are treated at a faster fluid removal rate, they begin to experience symptomatic hypotension. A mismatch occurs when the ultrafiltration rate exceeds the plasma refilling rate. Typically, vascular tone, a compensatory mechanism, increases to offset this mismatch but not all individuals have a functioning compensatory mechanism.
Hypotension is the manifestation of hypovolemia or a severe fluid imbalance, especially when there is a failure to activate compensatory mechanisms, such as individuals with anatomical neuropathy who lack responsive vascular tone. Symptomatically, hypotension may be experienced by the patient first as light-headedness. To monitor patients for hypotension, non-invasive blood pressure monitors are commonly used during RRT. When detected early, hypotension resulting from the excessive loss of fluid is easily reversed by giving the patient intravenous fluids. Following administering fluids the RRT operator can adjust the ultrafiltration rate to make the RRT treatment less aggressive.
Ultrafiltration controllers were developed specifically to reduce the occurrence of hypotension in dialysis patients. Ultrafiltration controllers can be based on approximation from the known trans-membrane pressure, volume based or gravity based. Roller pumps and weight scales are used in the latter to meter fluids. Ultrafiltration controllers ensure the rate of fluid removal from a patient's blood is close to the fluid removal setting that was selected by the operator. However, these controllers do not always protect the patient from hypotension. For example, the operator may set the fluid removal rate too high. If the operator setting is higher than the patient's fluid replenishing rate, the operator should reduce the rate setting when the signs of hypotension manifest. If the excessive rate is not reduced, the patient may still suffer from hypotension, even while the controller operates properly. Reddan D N, Szczech L A, Hasselblad V, Lowrie E G, Lindsay R M, Himmelfarb J, Toto R D, Stivelman J, Winchester J F, Zillman L A, Califf R M, Owen W F Jr. Intradialytic Blood Volume Monitoring in Ambulatory Hemodialysis patients: A Randomized Trial. Journal of the American Society of Nephrology. 2005; 16:2162-9
Attempts were made during the last two decades to develop monitors that could be used for feedback control of dialysis machine parameters, such as dialysate concentration, temperature, and ultrafiltration rate and ultrafiltrate volume. Blood volume feedback signals have been proposed that are based on optical measurements of hematocrit, blood viscosity and blood conductivity (impedance). Real-time control devices have been proposed that adjust the ultrafiltration rate to maintain a constant blood volume, and thereby balance the fluid removal and fluid recruitment rates. None of these proposed designs led to significant commercialization owing to the high cost of sensors, high signal to noise ratio or lack of economic incentive for manufacturers. In addition, many of these proposed systems required monitoring of patients by highly trained personnel.
The danger of hypotension as a consequence of excessive fluid removal during dialysis and other extracorporeal blood treatments has been recognized. U.S. Pat. No. 5,346,472 describes a control system to prevent hypotension that automatically adjusts the sodium concentration added to the dialysate by infusing a hypertonic or isotonic saline solution in response to operator input or patient's request based on symptoms. European patent EU 0311709 to Levin and Zasuwa describes automatic ultrafiltration feedback based on arterial blood pressure and heart rate. U.S. Pat. No. 4,710,164 describes an automatic ultrafiltration feedback device based on arterial blood pressure and heart rate. U.S. Pat. No. 4,466,804 describes an extracorporeal circulation system with a blood oxygenator that manipulates the withdrawal of blood to maintain CVP constant. U.S. Pat. No. 5,938,938 describes an automatic dialysis machine that controls ultrafiltration rate based on weight loss or the calculated blood volume change. Late model AK200 dialysis machines from Gambro (Sweden) include an optional blood volume monitor called BVS or Blood Volume Sensor. This sensor is optical and in fact measures blood hematocrit, or the concentration of red blood cells, in blood. Since dialysis filter membranes are impermeable to blood cells, increased hematocrit signifies the reduction of the overall blood volume. The BVS sensor is included in a feedback to the machine and is used to help the operator assess the rate of fluid removal. However, as realized by the inventors, this and similar technology have failed to show clinical relevance due to failure to measure compensatory mechanisms and importance of regional (e.g. cerebral) blood flow.
More recent references have further focused on the danger of hypotension as a consequence of excessive fluid removal during dialysis and other extracorporeal blood treatments. U.S. Pat. No. 6,821,441 describes a method for blood purification by means of hemodialysis and/or hemofiltration wherein a blood parameter selected from trans-membrane pressure, hematocrit value and blood density is monitored to control the infusion rate of a substitution fluid into a patient's blood. U.S. Pat. No. 6,706,007 describes a system that non-invasively monitors blood oxygen levels to detect when hypotension is about to occur in a patient undergoing extracorporeal treatment of their blood. U.S. Pat. No. 6,689,083 describes a system that non-invasively monitors osmotic pressure across a filter membrane of a blood filter to detect when hypotension is about to occur in a patient undergoing extracorporeal treatment of their blood.